There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.
BACKGROUND AND OBJECTIVE. The lipophilic antioxidant vitamin E has been used for more than 50 years in clinical and experimental dermatology. However, although a large number of case reports were published, there is still a lack of controlled clinical studies providing a rationale for clinical indications and dosage. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion, and photoprotection of vitamin E in human skin have led to the development of numerous new formulations for use in cosmetics and skin care products.
In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse skin by treatments with acetone +/- occlusion, sodium dodecyl sulfate, or tape-stripping. As a chronic model for barrier disruption, we used essential fatty acid deficient mice. Epidermal keratins were determined by one- and two-dimensional gel electrophoresis, immunoblots, and anti-keratin antibodies in biopsy samples. In addition, the expression of the cornified envelope proteins loricrin and involucrin after barrier disruption was determined by specific antibodies in human skin. Acute as well as chronic barrier disruption resulted in the induction of the expression of keratins K6, K16, and K17. Occlusion after acute disruption led to a slight reduction of keratin K6 and K16 expression. Expression of basal keratins K5 and K14 was reduced after both methods of barrier disruption. Suprabasal keratin K10 expression was increased after acute barrier disruption and K1 as well as K10 expression was increased after chronic barrier disruption. Loricrin expression in mouse and in human skin was unchanged after barrier disruption. In contrast, involucrin expression, which was restricted to the granular and upper spinous layers in normal human skin, showed an extension to the lower spinous layers 24 h after acetone treatment. In summary, our results document that acute or chronic barrier disruption leads to expression of keratins K6, K16, and K17 and to a premature expression of involucrin. We suggest that the coordinated regulation of lipid, DNA, keratin, and involucrin synthesis is critical for epidermal permeability barrier function.
The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age.
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